EP1004592A1 - Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments - Google Patents
Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments Download PDFInfo
- Publication number
- EP1004592A1 EP1004592A1 EP99402907A EP99402907A EP1004592A1 EP 1004592 A1 EP1004592 A1 EP 1004592A1 EP 99402907 A EP99402907 A EP 99402907A EP 99402907 A EP99402907 A EP 99402907A EP 1004592 A1 EP1004592 A1 EP 1004592A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- formula
- compound
- compounds
- methyl
- ppm
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 0 C*(C)N1NCC=C1 Chemical compound C*(C)N1NCC=C1 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H17/00—Compounds containing heterocyclic radicals directly attached to hetero atoms of saccharide radicals
- C07H17/04—Heterocyclic radicals containing only oxygen as ring hetero atoms
- C07H17/08—Hetero rings containing eight or more ring members, e.g. erythromycins
Definitions
- the present invention relates to new derivatives of erythromycin, their preparation process and their application as drugs.
- salts of the present derivatives with mineral or organic acids we can cite the salts formed with acetic, propionic, trifluoroacetic acids, maleic, tartaric, methanesulfonic, benzenesulfonic, p-toluenesulfonic, hydrochloric, hydrobromic, hydroiodic, sulfuric, phosphoric and especially stearic, ethylsuccinic or laurylsulfonic acids.
- the alkyl radical, alkenyl or alkynyl is preferably a methyl radical, ethyl, propyl, isopropyl, n-butyl, isobutyl, terbutyl, decyl or dodecyl, vinyl, allyl, ethynyl, propynyl, propargyl, cyclobutyl, cyclopentyl or cyclohexyl.
- the aryl radical may be a phenyl radical or naphthyle.
- the substituted or unsubstituted heteroaryl radical can be the thienyl, furyl, pyrolyl, thiazolyl, oxazolyl radical, imidazolyle, thiadiazolyle, pyrazolyle or isopyrazolyle, a pyridyl, pyrimidyl, pyridazinyl or pyrazinyl radical or another indolyl, benzofurannyl, benzothiazyl or quinoline.
- aryl radicals can include one or several substituents chosen from groups mentioned above.
- a very specific subject of the invention is the compounds of formula (I) in which Z represents a hydrogen atom, those in which n represents the number 4, those in which the radical is substituted by a radical
- the invention particularly relates to the compounds of formula (I) in which Y represents an atom hydrogen.
- the products of general formula (I) have a very good antibiotic activity on gram bacteria ? such as staphylococci, streptococci, pneumococci.
- the compounds of the invention can therefore be used as drugs in the treatment of germ infections sensitive and especially, in that of staphylococcal diseases, such as staphylococcal septicemia, staphylococcal disease facial or skin malignancies, pyoderma, sores septic or suppurative, boils, carbuncles, phlegmons, erysipelas and acne, staphylococcal diseases such as angina acute primitive or post influenza, bronchopneumonia, pulmonary suppuration, streptococcal disease such as acute angina, ear infections, sinusitis, scarlet fever, pneumococcal diseases such as pneumonia, bronchitis; the brucellosis, diphtheria, gonococcal disease.
- staphylococcal diseases such as staphylococcal septicemia, staphylococcal disease facial or skin malignancies, pyoderma, sores septic or suppurative, boils, carbuncles,
- the products of the present invention are also active against infections caused by germs like Haemophilus influenzae, Rickettsies, Mycoplasma pneumoniae, Chlamydia, Legionella, Ureaplasma, Toxoplasma or germs of the genus Mycobacterium.
- the present invention therefore also has for its object, as medicines and, in particular antibiotic medicines, the products of formula (I) as defined above, as well as their addition salts with acids pharmaceutically acceptable minerals or organic.
- the subject of the invention is more particularly, by way of drugs, including antibiotic drugs, product of Example 1 and its pharmaceutically salts acceptable.
- the invention also relates to the compositions pharmaceuticals containing as active ingredient at least one drugs defined above.
- compositions can be administered by the buccal, rectal, parenteral or locally topical application to the skin and mucous membranes, but the preferred route of administration is the oral route.
- compositions pharmaceuticals can be solid or liquid and present in the pharmaceutical forms commonly used in human medicine, such as simple tablets or sugar-coated tablets, capsules, granules, suppositories, injections, ointments, creams, gels; they are prepared according to the usual methods.
- the or the active ingredients can be incorporated therein excipients usually used in these compositions pharmaceuticals, such as talc, gum arabic, lactose, starch, magnesium stearate, butter cocoa, aqueous vehicles or not, original fatty substances animal or vegetable, paraffinic derivatives, glycols, the various wetting, dispersing or emulsifying agents, conservatives.
- compositions can also be presented under form of a powder intended to be dissolved extemporaneously in a suitable vehicle, for example sterile water nonpyrogenic.
- the dose administered is variable depending on the condition treated, subject, route of administration and product considered. It can be, for example, understood between 50 mg and 3000 mg per day orally, in adults for the product of Example 1.
- the invention also relates to products new chemicals, compounds of formula (III) and more especially the compound of formula (III) whose preparation is given below in the experimental part.
- EXAMPLE 1 11,12-Dideoxy-3-de [(2,6-dideoxy-3-C-methyl-3-O-methyl-.alpha.-L-ribohexopyranosyl) oxy] -6-O-methyl-3 -oxo-12,11- [oxycarbonyl [[4- [3- (3-pyridinyl) -1H-pyrazol-1-yl] butyl] imino]] - erythromycin
- the reaction mixture is brought to reflux for 1 hour 30 minutes.
- the product obtained is chromatographed on silica eluting with a methylene chloride, methanol, ammonia 95-5-0.5 mixture. 3.59 g of product are obtained, melting at 143-145 ° C.
- Stage A 11-deoxy 10,11-didehydro 3-de [(2,6-dideoxy 3-0-methyl ⁇ -L-ribohexopyranosyl) oxy] 6-0-methyl 3-oxo erythromycin.
- Stage B 2'-trimethylsilyloxy of 11-deoxy 10,11-didehydro 3-of [(2,6-dideoxy 3-0-methyl ⁇ -L-ribohexopyranosyl) oxy] 6-0-methyl 3-oxo erythmycin.
- Stage C 2'-trimethylsilyloxy 2a-fluoro of 11-deoxy 10,11-didehydro 3- of [(2,6-dideoxy 3-0-methyl ⁇ -L-ribohexopyranosyl) oxy] 6-0-methyl 3-oxo erythromycin.
- Stage D 2 ⁇ -fluoro of 11-deoxy 10,11-didehydro 3- of [(2,6-dideoxy 3-0-methyl 3-0-methyl ⁇ -L-ribohexopyranosyl) oxy] 6-0-methyl 3- oxo erythromycin
- a mixture of 5.476 is stirred for 3 hours 30 minutes g of product from Example 2, 50 ml of THF and 11.2 ml of 1M tetrabutylammonium fluoride in THF.
- the product obtained is chromatographed on silica, eluting with an ammonia-containing CH2CL2-MeOH 99-1 mixture, then 98-2, 97-3, 96-4, 95-5.
- 2.452 g of product are obtained research.
- Stage E 2'-acetoxy 2 ⁇ -fluoro of 11-deoxy 10,11-didehydro 3- of [(2,6-dideoxy 3-0-methyl ⁇ -L-ribohexopyranosyl) oxy] 6-0-methyl 3-oxo erythromycin
- Stage F 2'-acetoxy 2 ⁇ -fluoro of 12- (oxycarbonylimidazol) 11-deoxy 10,11-didehydro 3- of [(2,6-dideoxy 3-C-methyl-3-0-methyl ⁇ -L-ribohexopyranosyl ) oxy] 6-0-methyl 3-oxo erythromycin
- the starting amine was prepared as in preparation 1 from the product prepared as indicated in the following diagram.
- a series of tubes is prepared in which the same quantity of sterile nutritive medium is distributed. Increasing quantities of the product to be studied are distributed in each tube, then each tube is seeded with a bacterial strain. After incubation for 24 hours in an oven at 37 ° C, the growth inhibition is assessed by transillumination, which makes it possible to determine the minimum inhibitory concentrations (MIC) expressed in micrograms / CM 3 . The following results were obtained with the product of Example 1: (reading after 24 hours). GRAM + bacterial strains S.aureus 011UC4 0.040 S.aureus 011UC4 + 50% serum 0.600 S.aureus 011B18c S.aureus 011GR12c S.aureus 011GO25i 0.600 S.
- Example 1 has in particular an interesting activity on the bacterial strains with gram - Haemophilus Influenzae 351HT3, 351CB12, 351CA1 and 351GR6.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biotechnology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Oncology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Communicable Diseases (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Abstract
Description
- la réaction du composé de formule (II) avec le composé de formule (III) a lieu au sein d'un solvant tel que par exemple l'acétonitrile, le diméthylformamide ou encore le tétrahydrofuranne, le diméthoxy éthane ou le diméthylsulfoxyde,
- l'hydrolyse de la fonction ester en 2' est réalisée à l'aide du méthanol ou de l'acide chlorhydrique aqueux,
- la salification est réalisée au moyen d'acides selon les procédés classiques.
RMN CDCl3 ppm
Numéro | 1H | Numéro | 1H |
1 | 1' | 4,28 | |
2 | 3,86 | 2' | 3,16 |
3 | 3' | 2,44 | |
4 | 3,07 | 4' | 1,67 - 1,23 |
5 | 4,21 | 5' | 3,52 |
6 | 5' Me | 1,24 | |
7 | 1,59 - 1,82 | N(Me)2 | 2,26 |
8 | 2,60 | NCH2 | 3,60 à 3,80 |
9 | CH2 | 1,65 | |
10 | 3,13 | CH2 | 1,95 |
11 | 3,57 | CH2N | 4,21 |
12 | Pyrazole H4 | 6,55 | |
13 | 4,94 | Pyrazole H5 | 7,47 |
14 | 1,95 - 1,57 | pyridine | |
15 | 0,85 | H2 | 9,00 |
2Me | 1,36 | H4 | 8,11 |
4Me | 1,31 | H5 | 7,31 |
6Me | 1,33 ou 1,47 | H6 | 8,51 |
8Me | 1,16 | ||
lOMe | 1,00 | ||
12Me | 1,33 ou 1,47 | ||
60Me | 2,60 |
Spectre de masse MH+=812+
Spectre RMN (300MHz dans CDCl3)
H2 : 3.84 ppm ; H4 : 3006 ppm ; H5 : 4.22 ppm ; H7 : 1.58 1.83 ppm ; H8 : 2.58 ppm ; H10 : 3.12 ppm ; H11 : 3.56 ppm ; H13 : 4.92 ppm ; H14 : 1.551.94 ; H15 : 0.81ppm ; 2Me : 1.35 ppm ; 4Me 1.29 ppm ; 6 Me : 1.32 ou 1.46 ppm ; 8 Me 1.16 ppm ; 10 Me : 1.01ppm ; 12 Me : 1.32 ou 1.46 ppm ; 60 Me : 2.6 ppm ; 1' : 4.27 ppm ; 2' : 3.17 ppm ; 3' 2.44 ppm ; 4' : 1.67 et 1.24 ppm ; 5' : 3.55 ppm ; Nme2 : 2.26 ppm ; NCH2 : 3.69 ppm ; CH2 : 1.64 1.94 ppm ; CH2N : 4.19 ppm ; pyrazole : 7.77 ppm ; pyridine : 8.76 7.75 7.27 8.44 ppm.
Spectre de masse
812+ : MH+
850+ : MK+
H4 : 3.53 ppm ; H5 : 4.05 ppm ; H7 : 1.51 1.88 ppm ; H8 : 2.61ppm ; H10 : 3.10 ppm ; Hll : 3.42 ppm ; H13 : 4.86 ppm ; H14 : 1.631.95 ; H15 : 0.85 ppm ; 2Me : 1.75 ppm ; 4Me : 1.29 ppm ; 6 Me : 1.31 ou 1.49 ppm ; 8Me : 1.17 ppm ; lOMe : 1.00 ppm ; 12Me : 1.31 ou 1.49 ppm ; 60Me : 2.51 ppm ; 1' : 4.30 ppm ; 2' : 3.19 ppm ; 3' : 2.48 ppm ; 4' : 1.68 et 1.26 ppm ; 5' : 3.53 ppm ; 5'Me : 1.24 ppm ; Nme2 : 2.28 ppm ; NCH2 : 3.55 à 3.80 ppm ; CH2 : 1.61 1.93 ppm ; CH2N : 4.19 ppm ; pyrazole : 7.75 7.78 ppm ; pyridine : 8.77 7.77 7.27 8.44 ppm
Spectre de masse
830+ : MH+
158+ : Désosamine
673+ : 830+ -158+H
Produit de l'exemple 1 | 150 mg |
Excipient q.s.p. | 1 g |
Souches bactériennes à GRAM+ | ||
S.aureus | 011UC4 | 0.040 |
S.aureus | 011UC4+sérum 50% | 0.600 |
S.aureus | 011B18c | |
S.aureus | 011GR12c | |
S.aureus | 011GO25i | 0.600 |
S.epidermidis | 012GO11i | 0.040 |
S.aureus | 011CB20c | |
S.epidermidis | 012GO40c | |
S. pyogenes | 02A1UC1 | 0.02 |
S. agalactiae | 02B1HT1 | 0.02 |
S. faecalis | 02D2UC1 | 0.02 |
S. faecium | 02D3HT1 | 0.02 |
Streptococcus gr.G | 02GOGR5 | 0.02 |
S. mitis | 02MitCB1 | 0.02 |
S. agalactiae | 02B1SJ1c | 0.050 |
S. faecalis | 02D2DU15c | 5.000 |
Streptococcus gr.G | 02Gogr4c | |
S. sanguis | 02SGr10i | 0.02 |
S. mitis | 02MitGR16i | 0.02 |
S. pneumoniae | 032UC1 | 0.02 |
S. pneumoniae | 030GR20 | 0.02 |
S. pneumoniae | 030SJ5i | 0.040 |
S. pneumoniae | 030CR18c | 0.300 |
S. pneumoniae | 030PW23c | 0.02 |
S. pneumoniae | 030RO1i | 0.150 |
S. pneumoniae | 030SJ1c | 0.150 |
Claims (12)
- Les composés de formule (I) dans laquelleY représente un atome d'hydrogène ou un atome de fluor,n représente un nombre entier compris entre 1 et 8,Z représente un atome d'hydrogène ou le reste d'un acide carboxylique,
- Les composés de formule (I) définis à la revendication 1 dans lesquels Z représente un atome d'hydrogène.
- Les composés de formule (I) définis à la revendication 1 ou 2 dans lesquels n représente le nombre 4.
- Le composé de formule (I) défini à la revendication 1 dans laquelle Y représente un atome d'hydrogène.
- Le composé de formule répondant à la formule (I) de la revendication 1 suivant : 11,12-didéoxy-3-de [(2,6-didéoxy-3-C-méthyl-3-O-méthyl-.alpha.-L-ribohexopyranosyl)oxy]-6-O-méthyl-3-oxo-12,11- [oxycarbonyl[[4-[3-(3-pyridinyl)-1H-pyrazol-1-yl]butyl]imino]]-érythromycine.
- A titre de médicaments les composés de formule (I) définis à l'une quelconque des revendications 1 à 5 ainsi que leurs sels d'addition avec les acides pharmaceutiquement acceptables.
- A titre de médicaments, le composé de formule (I) défini à la revendication 6 ainsi que ses sels d'addition avec les acides pharmaceutiquement acceptables.
- Les compositions pharmaceutiques renfermant comme principe actif au moins un médicament selon la revendication 7 ou 8.
- Procédé de préparation des composés de formule (I) définis à l'une quelconque des revendications 1 à 6 caractérisé en ce que l'on soumet un composé de formule (II) dans laquelle Y conserve sa signification précédente et M représente le reste d'un acide à l'action d'un composé de formule (III) dans lequel le radical hétérocyclique peut-être substitué pour obtenir le composé de formule (IA) dans lequel Z représente le reste d'un acide, puis si désiré soumet ce composé de formule (IA) à l'action d'un agent de libération de l'hydroxyle en 2' pour obtenir le composé de formule (IB) correspondant dans lequel Z représente un atome d'hydrogène que l'on soumet si désiré à l'action d'un acide pour en former le sel.
- A titre de produits chimiques nouveaux, les composés de formule (III) définis à la revendication 10.
- A titre de produit chimique nouveau défini à la revendication 11, les composés de formule (III) suivants : 3-(3-pyridinyl)-1H-pyrazole-1-butanamine, 4-(3-pyridinyl)-1H-pyrazole-1-butanamine.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR9814782A FR2786188B1 (fr) | 1998-11-24 | 1998-11-24 | Nouveaux derives de l'erythromycine, leur procede de preparation et leur applicaion comme medicaments |
FR9814782 | 1998-11-24 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP1004592A1 true EP1004592A1 (fr) | 2000-05-31 |
EP1004592B1 EP1004592B1 (fr) | 2003-07-16 |
Family
ID=9533122
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP99402907A Expired - Lifetime EP1004592B1 (fr) | 1998-11-24 | 1999-11-23 | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments |
Country Status (24)
Country | Link |
---|---|
US (2) | US6440941B1 (fr) |
EP (1) | EP1004592B1 (fr) |
JP (1) | JP2000159790A (fr) |
KR (1) | KR100587445B1 (fr) |
CN (1) | CN1165546C (fr) |
AR (1) | AR021388A1 (fr) |
AT (1) | ATE245160T1 (fr) |
AU (1) | AU772171B2 (fr) |
BR (1) | BR9905735A (fr) |
CA (1) | CA2290136C (fr) |
DE (1) | DE69909577T2 (fr) |
DK (1) | DK1004592T3 (fr) |
ES (1) | ES2198867T3 (fr) |
FR (1) | FR2786188B1 (fr) |
HU (1) | HUP9904392A3 (fr) |
IL (1) | IL133101A (fr) |
MX (1) | MXPA99010813A (fr) |
NO (1) | NO314729B1 (fr) |
PL (1) | PL336736A1 (fr) |
PT (1) | PT1004592E (fr) |
RU (1) | RU2237672C2 (fr) |
TR (1) | TR199902888A2 (fr) |
TW (1) | TWI247747B (fr) |
ZA (1) | ZA997176B (fr) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000044761A2 (fr) * | 1999-01-27 | 2000-08-03 | Pfizer Products Inc. | Antibiotiques cetolides |
US6777543B2 (en) | 1999-05-24 | 2004-08-17 | Pfizer, Inc. | 13-methyl erythromycin derivatives |
FR2862647A1 (fr) * | 2003-11-25 | 2005-05-27 | Aventis Pharma Sa | Derives de pyrazolyle, procede de preparation et intermediaires de ce procede a titre de medicaments et de compositions pharmaceutiques les renfermant |
WO2012052412A1 (fr) | 2010-10-22 | 2012-04-26 | Bayer Cropscience Ag | Nouveaux composés hétérocycliques utilisés en tant qu'agents pour lutter contre des nuisibles |
Families Citing this family (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2786188B1 (fr) * | 1998-11-24 | 2002-10-31 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur applicaion comme medicaments |
DK1167376T3 (da) | 2000-06-30 | 2004-10-25 | Pfizer Prod Inc | Makrolidantibiotika |
EP1638549A4 (fr) | 2003-03-10 | 2011-06-15 | Optimer Pharmaceuticals Inc | Nouveaux agents antibacteriens |
JP2008508322A (ja) * | 2004-07-28 | 2008-03-21 | ランバクシー ラボラトリーズ リミテッド | 抗菌剤としてのケトライド誘導体 |
AU2008316830B2 (en) | 2007-10-25 | 2016-03-17 | Cempra Pharmaceuticals, Inc. | Process for the preparation of macrolide antibacterial agents |
WO2009137787A1 (fr) | 2008-05-09 | 2009-11-12 | Enanta Pharmaceuticals, Inc. | Procédés pour la préparation de dérivés d’érythromycine 2-fluoro-6-11-bicycliques |
JP5602748B2 (ja) | 2008-10-24 | 2014-10-08 | センプラ ファーマシューティカルズ,インコーポレイテッド | トリアゾール含有マクロライドを用いた生体防御 |
US9937194B1 (en) | 2009-06-12 | 2018-04-10 | Cempra Pharmaceuticals, Inc. | Compounds and methods for treating inflammatory diseases |
CN102724874B (zh) | 2009-09-10 | 2018-06-01 | 森普拉制药公司 | 治疗疟疾、结核病和mac疾病的方法 |
KR102006200B1 (ko) | 2010-03-22 | 2019-08-01 | 셈프라 파마슈티컬스, 인크. | 매크로라이드의 결정 형태들 및 그 용도들 |
ES2636948T3 (es) | 2010-05-20 | 2017-10-10 | Cempra Pharmaceuticals, Inc. | Procesos para preparar macrólidos y cetólidos e intermediarios para los mismos |
JP6042334B2 (ja) * | 2010-09-10 | 2016-12-14 | センプラ ファーマシューティカルズ,インコーポレイテッド | 疾患治療のための水素結合形成フルオロケトライド |
CA2868262A1 (fr) | 2012-03-27 | 2013-10-03 | Cempra Pharmaceuticals, Inc. | Formulations parenterales pour l'administration d'antibiotiques macrolides |
EP2968801B1 (fr) | 2013-03-14 | 2018-09-26 | Cempra Pharmaceuticals, Inc. | Procédés pour traiter des maladies respiratoires et formulations pour la mise en oeuvre de ceux-ci |
EP2968384A4 (fr) | 2013-03-15 | 2017-02-15 | Cempra Pharmaceuticals, Inc. | Procédés convergents de préparation d'agents antibactériens macrolides |
CN106432383A (zh) * | 2016-09-14 | 2017-02-22 | 重庆两江药物研发中心有限公司 | 索利霉素及其中间体的制备方法 |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2756852A1 (de) * | 1976-12-20 | 1978-06-22 | Sterling Drug Inc | 1-amino-niedrig-alkyl-3,4-diphenyl- 1h-pyrazole |
JPH04234891A (ja) * | 1990-03-05 | 1992-08-24 | Fujisawa Pharmaceut Co Ltd | 新規セフェム化合物およびその塩 |
EP0596802A1 (fr) * | 1992-11-05 | 1994-05-11 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation, leur application comme médicaments |
GB2288174A (en) * | 1994-04-08 | 1995-10-11 | Roussel Uclaf | Erythromycin derivatives, processes for preparing them, pharmaceutical compositions containing them, and their use as medicaments |
WO1998056800A1 (fr) * | 1997-06-11 | 1998-12-17 | Pfizer Products Inc. | Derives de 9-oxime erythromycine |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4182895A (en) * | 1976-12-20 | 1980-01-08 | Sterling Drug Inc. | 1-Amino-lower-alkyl-3,4-diphenyl-1H-pyrazoles |
FR2719587B1 (fr) * | 1994-05-03 | 1996-07-12 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
FR2727969B1 (fr) * | 1994-12-09 | 1997-01-17 | Roussel Uclaf | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
FR2742757B1 (fr) * | 1995-12-22 | 1998-01-30 | Roussel Uclaf | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments |
FR2786188B1 (fr) * | 1998-11-24 | 2002-10-31 | Hoechst Marion Roussel Inc | Nouveaux derives de l'erythromycine, leur procede de preparation et leur applicaion comme medicaments |
-
1998
- 1998-11-24 FR FR9814782A patent/FR2786188B1/fr not_active Expired - Fee Related
-
1999
- 1999-11-16 TW TW088119939A patent/TWI247747B/zh not_active IP Right Cessation
- 1999-11-17 AU AU59522/99A patent/AU772171B2/en not_active Expired
- 1999-11-18 ZA ZA9907176A patent/ZA997176B/xx unknown
- 1999-11-18 US US09/442,681 patent/US6440941B1/en not_active Expired - Lifetime
- 1999-11-18 CA CA2290136A patent/CA2290136C/fr not_active Expired - Lifetime
- 1999-11-22 JP JP11331141A patent/JP2000159790A/ja active Pending
- 1999-11-23 EP EP99402907A patent/EP1004592B1/fr not_active Expired - Lifetime
- 1999-11-23 KR KR1019990052014A patent/KR100587445B1/ko active IP Right Grant
- 1999-11-23 MX MXPA99010813A patent/MXPA99010813A/es active IP Right Grant
- 1999-11-23 DE DE69909577T patent/DE69909577T2/de not_active Expired - Lifetime
- 1999-11-23 RU RU99125547A patent/RU2237672C2/ru not_active IP Right Cessation
- 1999-11-23 PT PT99402907T patent/PT1004592E/pt unknown
- 1999-11-23 AT AT99402907T patent/ATE245160T1/de active
- 1999-11-23 CN CNB99127394XA patent/CN1165546C/zh not_active Expired - Lifetime
- 1999-11-23 HU HU9904392A patent/HUP9904392A3/hu unknown
- 1999-11-23 ES ES99402907T patent/ES2198867T3/es not_active Expired - Lifetime
- 1999-11-23 NO NO19995745A patent/NO314729B1/no unknown
- 1999-11-23 DK DK99402907T patent/DK1004592T3/da active
- 1999-11-23 IL IL133101A patent/IL133101A/en not_active IP Right Cessation
- 1999-11-24 BR BR9905735-2A patent/BR9905735A/pt active Search and Examination
- 1999-11-24 AR ARP990105985A patent/AR021388A1/es not_active Application Discontinuation
- 1999-11-24 TR TR1999/02888A patent/TR199902888A2/xx unknown
- 1999-11-24 PL PL99336736A patent/PL336736A1/xx not_active Application Discontinuation
-
2002
- 2002-07-02 US US10/188,394 patent/US6664398B2/en not_active Expired - Lifetime
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2756852A1 (de) * | 1976-12-20 | 1978-06-22 | Sterling Drug Inc | 1-amino-niedrig-alkyl-3,4-diphenyl- 1h-pyrazole |
JPH04234891A (ja) * | 1990-03-05 | 1992-08-24 | Fujisawa Pharmaceut Co Ltd | 新規セフェム化合物およびその塩 |
EP0596802A1 (fr) * | 1992-11-05 | 1994-05-11 | Roussel Uclaf | Nouveaux dérivés de l'érythromycine, leur procédé de préparation, leur application comme médicaments |
GB2288174A (en) * | 1994-04-08 | 1995-10-11 | Roussel Uclaf | Erythromycin derivatives, processes for preparing them, pharmaceutical compositions containing them, and their use as medicaments |
WO1998056800A1 (fr) * | 1997-06-11 | 1998-12-17 | Pfizer Products Inc. | Derives de 9-oxime erythromycine |
Non-Patent Citations (4)
Title |
---|
A.S.POGOSYAN ET AL.: "Alkylation of Azoles by beta-functionality Substituted Alkyl Halides under Phase-Transfer Catalysis Conditions.", ZH. PRIKL. KHIM., vol. 59, no. 6, 1985, pages 1296 - 1300, XP002112559 * |
DATABASE WPI Section Ch Week 9240, Derwent World Patents Index; Class B02, AN 92-327578, XP002112560 * |
E.POMARNACKA ET AL.: "Synthesis and Hypoglycemic Properties of some N-((alkyl-1-pyrazolyl)alkyl)biguanides.", ACTA POL. PHARM., vol. 42, no. 3, 1985, pages 236 - 239, XP002112558 * |
R.FERRONI ET AL.: "Synthesis and Platelet Aggregation Inhibitory Effects of N-((1H-Pyrazol-1-yl)alkyl)benzoylamides.", ARZNEIM. FORSCH., vol. 40, no. 6, 1990, pages 705 - 709, XP002112557 * |
Cited By (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000044761A2 (fr) * | 1999-01-27 | 2000-08-03 | Pfizer Products Inc. | Antibiotiques cetolides |
WO2000044761A3 (fr) * | 1999-01-27 | 2001-01-04 | Pfizer Prod Inc | Antibiotiques cetolides |
US6777543B2 (en) | 1999-05-24 | 2004-08-17 | Pfizer, Inc. | 13-methyl erythromycin derivatives |
FR2862647A1 (fr) * | 2003-11-25 | 2005-05-27 | Aventis Pharma Sa | Derives de pyrazolyle, procede de preparation et intermediaires de ce procede a titre de medicaments et de compositions pharmaceutiques les renfermant |
WO2005051917A1 (fr) * | 2003-11-25 | 2005-06-09 | Aventis Pharma S.A. | Derives de pyrazole a titre de medicaments pour le traitement des degenerescences neuronales aigues ou chroniques |
US7524838B2 (en) | 2003-11-25 | 2009-04-28 | Aventis Pharma S.A. | Pyrazolyl derivatives, preparation process and intermediates of this process as medicinal products and pharmaceutical compositions containing them |
AU2004293214B2 (en) * | 2003-11-25 | 2011-04-21 | Aventis Pharma S.A. | Pyrazolyl derivatives in the form of drugs for treating acute or chronic neuronal regressions |
US8048893B2 (en) | 2003-11-25 | 2011-11-01 | Aventis Pharma Sa | Pyrazolyl derivatives, preparation process and intermediates of this process as medicinal products and pharmaceutical compositions containing them |
WO2012052412A1 (fr) | 2010-10-22 | 2012-04-26 | Bayer Cropscience Ag | Nouveaux composés hétérocycliques utilisés en tant qu'agents pour lutter contre des nuisibles |
US9173396B2 (en) | 2010-10-22 | 2015-11-03 | Bayer Intellectual Property Gmbh | Heterocyclic compounds as pesticides |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
EP0606024B1 (fr) | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments | |
EP0799833B1 (fr) | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments | |
CA2290136C (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
CA2102457C (fr) | Derives de l'erythromycine, leur procede de preparation, leur application comme medicaments | |
CA2350651C (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
EP0885234B1 (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
EP1026170B1 (fr) | Nouveaux dérivés de l'erythromycine, leur procédé de préparation et leur application comme médicaments | |
EP0974598B1 (fr) | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments | |
FR2692579A1 (fr) | Nouveaux dérivés de la picromycine, leur procédé de préparation et leur application comme médicaments. | |
EP0931088B1 (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
EP0906326B1 (fr) | Nouveaux derives aromatiques substitues par un ribose, leur procede de preparation et leur application comme medicaments | |
EP0946579B1 (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
EP1000952B1 (fr) | Nouveaux dérivés 2-halogénés de 5-0-désosaminylérythronolide A, leur procédé de préparation et leur application comme médicaments | |
EP0946580B1 (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
EP0894805B1 (fr) | Nouveaux dérivés aromatiques substitués par un ribose, leur procédé de préparation et leur application comme médicaments | |
EP1098901B1 (fr) | Nouveaux derives de la 6-deoxy erythromycine, leur procede de preparation et leur application comme medicaments | |
CA2247175C (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
FR2792637A1 (fr) | Nouveaux derives de l'erythromycine, leur procede de preparation et leur application comme medicaments | |
FR2697523A1 (fr) | Nouveaux dérivés de l'érythromycine, leur procédé de préparation et leur application comme médicaments. |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
AX | Request for extension of the european patent |
Free format text: AL;LT;LV;MK;RO;SI |
|
17P | Request for examination filed |
Effective date: 20001130 |
|
AKX | Designation fees paid |
Free format text: AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
RAP1 | Party data changed (applicant data changed or rights of an application transferred) |
Owner name: AVENTIS PHARMA S.A. |
|
17Q | First examination report despatched |
Effective date: 20011001 |
|
GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
GRAH | Despatch of communication of intention to grant a patent |
Free format text: ORIGINAL CODE: EPIDOS IGRA |
|
GRAA | (expected) grant |
Free format text: ORIGINAL CODE: 0009210 |
|
AK | Designated contracting states |
Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: FG4D Free format text: NOT ENGLISH |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: EP |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: FG4D Free format text: FRENCH |
|
REF | Corresponds to: |
Ref document number: 69909577 Country of ref document: DE Date of ref document: 20030821 Kind code of ref document: P |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: NV Representative=s name: A. BRAUN, BRAUN, HERITIER, ESCHMANN AG PATENTANWAE |
|
REG | Reference to a national code |
Ref country code: GR Ref legal event code: EP Ref document number: 20030403133 Country of ref document: GR |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: LU Payment date: 20031015 Year of fee payment: 5 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: CY Payment date: 20031017 Year of fee payment: 5 |
|
GBT | Gb: translation of ep patent filed (gb section 77(6)(a)/1977) |
Effective date: 20031006 |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: TRGR |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: MC Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20031130 |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FG2A Ref document number: 2198867 Country of ref document: ES Kind code of ref document: T3 |
|
PLBE | No opposition filed within time limit |
Free format text: ORIGINAL CODE: 0009261 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT |
|
26N | No opposition filed |
Effective date: 20040419 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: LU Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20041123 Ref country code: CY Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20041123 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PFA Owner name: AVENTIS PHARMA S.A. Free format text: AVENTIS PHARMA S.A.#20, AVENUE RAYMOND ARON#92160 ANTONY (FR) -TRANSFER TO- AVENTIS PHARMA S.A.#20, AVENUE RAYMOND ARON#92160 ANTONY (FR) |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20121123 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PCAR Free format text: NEW ADDRESS: HOLBEINSTRASSE 36-38, 4051 BASEL (CH) |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 17 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 18 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: IT Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES Effective date: 20121123 |
|
PGRI | Patent reinstated in contracting state [announced from national office to epo] |
Ref country code: IT Effective date: 20161118 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 19 |
|
REG | Reference to a national code |
Ref country code: FR Ref legal event code: PLFP Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: BE Payment date: 20180914 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: NL Payment date: 20181114 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: GR Payment date: 20181011 Year of fee payment: 20 Ref country code: SE Payment date: 20181113 Year of fee payment: 20 Ref country code: PT Payment date: 20181121 Year of fee payment: 20 Ref country code: DK Payment date: 20181109 Year of fee payment: 20 Ref country code: AT Payment date: 20181025 Year of fee payment: 20 Ref country code: IE Payment date: 20181109 Year of fee payment: 20 Ref country code: FI Payment date: 20181109 Year of fee payment: 20 Ref country code: DE Payment date: 20181113 Year of fee payment: 20 |
|
PGFP | Annual fee paid to national office [announced via postgrant information from national office to epo] |
Ref country code: IT Payment date: 20181122 Year of fee payment: 20 Ref country code: ES Payment date: 20181203 Year of fee payment: 20 Ref country code: FR Payment date: 20181011 Year of fee payment: 20 Ref country code: CH Payment date: 20181115 Year of fee payment: 20 Ref country code: GB Payment date: 20181121 Year of fee payment: 20 |
|
REG | Reference to a national code |
Ref country code: DE Ref legal event code: R071 Ref document number: 69909577 Country of ref document: DE |
|
REG | Reference to a national code |
Ref country code: DK Ref legal event code: EUP Effective date: 20191123 |
|
REG | Reference to a national code |
Ref country code: NL Ref legal event code: MK Effective date: 20191122 |
|
REG | Reference to a national code |
Ref country code: CH Ref legal event code: PL |
|
REG | Reference to a national code |
Ref country code: BE Ref legal event code: MK Effective date: 20191123 |
|
REG | Reference to a national code |
Ref country code: GB Ref legal event code: PE20 Expiry date: 20191122 |
|
REG | Reference to a national code |
Ref country code: IE Ref legal event code: MK9A |
|
REG | Reference to a national code |
Ref country code: AT Ref legal event code: MK07 Ref document number: 245160 Country of ref document: AT Kind code of ref document: T Effective date: 20191123 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: PT Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20191205 Ref country code: GB Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20191122 Ref country code: IE Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20191123 |
|
REG | Reference to a national code |
Ref country code: SE Ref legal event code: EUG |
|
REG | Reference to a national code |
Ref country code: ES Ref legal event code: FD2A Effective date: 20200724 |
|
PG25 | Lapsed in a contracting state [announced via postgrant information from national office to epo] |
Ref country code: ES Free format text: LAPSE BECAUSE OF EXPIRATION OF PROTECTION Effective date: 20191124 |